tbuckley/cabot-search huggingface dataset:
Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline
Authors: Manish A. Shah, Erin B. Kennedy, Ashley E. Alarcon-Rozas, Thierry Alcindor, Angela N. Bartley, Aubrey Belk Malowany, Nishin A. Bhadkamkar, Dana C. Deighton, Yelena Janjigian, Asha Karippot, Uqba Khan, Daniel A. King, Kelsey Klute, Jill Lacy, James J. Lee, Rutika Mehta, Sarbajit Mukherjee, Arun Nagarajan, Haeseong Park, Anwaar Saeed, Thomas J. Semrad, Kohei Shitara, Elizabeth Smyth, Nataliya V. Uboha, Melani Vincelli, Zev Wainberg, Lakshmi Rajdev
Journal: Journal of Clinical Oncology (2023)

To develop recommendations involving targeted therapies for patients with advanced gastroesophageal cancer.The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.Eighteen randomized controlled trials met the inclusion criteria for the systematic review.For human epidermal growth factor receptor 2 (HER2)-negative patients with gastric adenocarcinoma (AC) and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 5, first-line therapy with nivolumab and chemotherapy (CT) is recommended. For HER2-negative patients with esophageal or gastroesophageal junction (GEJ) AC and PD-L1 CPS ≥ 5, first-line therapy with nivolumab and CT is recommended. First-line therapy with pembrolizumab and CT is recommended for HER2-negative patients with esophageal or GEJ AC and PD-L1 CPS ≥ 10. For patients with esophageal squamous cell carcinoma and PD-L1 tumor proportion score ≥ 1%, nivolumab plus CT, or nivolumab plus ipilimumab is recommended; for patients with esophageal squamous cell carcinoma and PD-L1 CPS ≥ 10, pembrolizumab plus CT is recommended. For patients with HER2-positive gastric or GEJ previously untreated, unresectable or metastatic AC, trastuzumab plus pembrolizumab is recommended, in combination with CT. For patients with advanced gastroesophageal or GEJ AC whose disease has progressed after first-line therapy, ramucirumab plus paclitaxel is recommended. For HER2-positive patients with gastric or GEJ AC who have progressed after first-line therapy, trastuzumab deruxtecan is recommended. In all cases, participation in a clinical trial is recommended as it is the panel's expectation that targeted treatment options for gastroesophageal cancer will continue to evolve.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
Central nervous system status is prognostic in T-cell acute lymphoblastic leukemia: a Children’s Oncology Group report
Authors: Nathan P. Gossai, Meenakshi Devidas, Zhiguo Chen, Brent L. Wood, Patrick A. Zweidler-McKay, Karen R. Rabin, Mignon L. Loh, Elizabeth A. Raetz, Naomi J. Winick, Michael J. Burke, Andrew J. Carroll, Natia Esiashvili, Nyla A. Heerema, William L. Carroll, Stephen P. Hunger, Kimberly P. Dunsmore, Stuart S. Winter, David T. Teachey
Journal: Blood (2023)
Sequential Targeting of Retinoblastoma and DNA Synthesis Pathways Is a Therapeutic Strategy for Sarcomas That Can Be Monitored in Real Time
Authors: Tuyen Duong Thanh Nguyen, Yan Wang, Tuyen N. Bui, Rossana Lazcano, Davis R. Ingram, Min Yi, Varshini Vakulabharanam, Linjie Luo, Marc A. Pina, Cansu Karakas, Mi Li, Nicole M. Kettner, Neeta Somaiah, Peter J. Hougton, Osama Mawlawi, Alexander J. Lazar, Kelly K. Hunt, Khandan Keyomarsi
Journal: Cancer Research (2023)

Abstract Treatment strategies with a strong scientific rationale based on specific biomarkers are needed to improve outcomes in patients with advanced sarcomas. Suppression of cell-cycle progression through reactivation of the tumor suppressor retinoblastoma (Rb) using CDK4/6 inhibitors is a potential avenue for novel targeted therapies in sarcomas that harbor intact Rb signaling. Here, we evaluated combination treatment strategies (sequential and concomitant) with the CDK4/6 inhibitor abemacicib to identify optimal combination strategies. Expression of Rb was examined in 1,043 sarcoma tumor specimens, and 50% were found to be Rb-positive. Using in vitro and in vivo models, an effective two-step sequential combination strategy was developed. Abemaciclib was used first to prime Rb-positive sarcoma cells to reversibly arrest in G1 phase. Upon drug removal, cells synchronously traversed to S phase, where a second treatment with S-phase targeted agents (gemcitabine or Wee1 kinase inhibitor) mediated a synergistic response by inducing DNA damage. The response to treatment could be noninvasively monitored using real-time positron emission tomography imaging and serum thymidine kinase activity. Collectively, these results show that a novel, sequential treatment strategy with a CDK4/6 inhibitor followed by a DNA-damaging agent was effective, resulting in synergistic tumor cell killing. This approach can be readily translated into a clinical trial with noninvasive functional imaging and serum biomarkers as indicators of response and cell cycling. Significance: An innovative sequential therapeutic strategy targeting Rb, followed by treatment with agents that perturb DNA synthesis pathways, results in synergistic killing of Rb-positive sarcomas that can be noninvasively monitored.
Radial Sponges Facilitate Wound Healing by Promoting Cell Migration and Angiogenesis
Authors: Jiawen Li, Lingfei Xiao, Shijie Gao, Huayi Huang, Qingjian Lei, Yan Chen, Zhe Chen, Longjian Xue, Feifei Yan, Lin Cai
Journal: Advanced Healthcare Materials (2023)

Abstract The topographic cues of wound dressings play important roles in regulating cellular behaviors, such as cellular migration and morphology, and are capable of providing a prolonged stimulus for promoting wound healing. However, 3D porous dressings that can guide wound healing from the periphery to the center are poorly studied. Herein, radial sponges with adjustable lamellar spacing and microridge spacing by ice templating are developed to facilitate wound healing. With denser lamellae and microridges, fibroblasts achieve a more orderly arrangement, a larger elongation, and a greater migration rate. Meanwhile, the elongated state enables human umbilical vein endothelial cells to vascularization. The faster healing rate and a higher degree of vascularization based on radial sponges are further demonstrated in full‐thickness skin defects in rats. Taken together, radial sponges with the densest lamellae and microridges perform the best in guiding the wound from the periphery to the center of the repair environment. It is believed that the proposed structure here can be combined with various biochemical factors to provide dressings with functions.
<i>BMPR2</i> Mutation and Metabolic Reprogramming in Pulmonary Arterial Hypertension
Authors: Iona Cuthbertson, Nicholas W. Morrell, Paola Caruso
Journal: Circulation Research (2023)

Pulmonary arterial hypertension forms the first and most severe of the 5 categories of pulmonary hypertension. Disease pathogenesis is driven by progressive remodeling of peripheral pulmonary arteries, caused by the excessive proliferation of vascular wall cells, including endothelial cells, smooth muscle cells and fibroblasts, and perivascular inflammation. Compelling evidence from animal models suggests endothelial cell dysfunction is a key initial trigger of pulmonary vascular remodeling, which is characterised by hyperproliferation and early apoptosis followed by enrichment of apoptosis-resistant populations. Dysfunctional pulmonary arterial endothelial cells lose their ability to produce vasodilatory mediators, together leading to augmented pulmonary arterial smooth muscle cell responses, increased pulmonary vascular pressures and right ventricular afterload, and progressive right ventricular hypertrophy and heart failure. It is recognized that a range of abnormal cellular molecular signatures underpin the pathophysiology of pulmonary arterial hypertension and are enhanced by loss-of-function mutations in the BMPR2 gene, the most common genetic cause of pulmonary arterial hypertension and associated with worse disease prognosis. Widespread metabolic abnormalities are observed in the heart, pulmonary vasculature, and systemic tissues, and may underpin heterogeneity in responsivity to treatment. Metabolic abnormalities include hyperglycolytic reprogramming, mitochondrial dysfunction, aberrant polyamine and sphingosine metabolism, reduced insulin sensitivity, and defective iron handling. This review critically discusses published mechanisms linking metabolic abnormalities with dysfunctional BMPR2 (bone morphogenetic protein receptor 2) signaling; hypothesized mechanistic links requiring further validation; and their relevance to pulmonary arterial hypertension pathogenesis and the development of potential therapeutic strategies.
Cardiac Alternans: From Bedside to Bench and Back
Authors: Zhilin Qu, James N. Weiss
Journal: Circulation Research (2023)

Cardiac alternans arises from dynamical instabilities in the electrical and calcium cycling systems of the heart, and often precedes ventricular arrhythmias and sudden cardiac death. In this review, we integrate clinical observations with theory and experiment to paint a holistic portrait of cardiac alternans: the underlying mechanisms, arrhythmic manifestations and electrocardiographic signatures. We first summarize the cellular and tissue mechanisms of alternans that have been demonstrated both theoretically and experimentally, including 3 voltage-driven and 2 calcium-driven alternans mechanisms. Based on experimental and simulation results, we describe their relevance to mechanisms of arrhythmogenesis under different disease conditions, and their link to electrocardiographic characteristics of alternans observed in patients. Our major conclusion is that alternans is not only a predictor, but also a causal mechanism of potentially lethal ventricular and atrial arrhythmias across the full spectrum of arrhythmia mechanisms that culminate in functional reentry, although less important for anatomic reentry and focal arrhythmias.
Multitarget Stool DNA Testing Has High Positive Predictive Value for Colorectal Neoplasia on the Second Round of Testing
Authors: Jordan K. Voss, Derek W. Ebner, Keli N. Burger, Douglas W. Mahoney, Mary E. Devens, Kari L. Lowrie, John B. Kisiel
Journal: Clinical Gastroenterology and Hepatology (2023)
Neutralisation sensitivity of the SARS-CoV-2 XBB.1 lineage
Authors: Prerna Arora, Anne Cossmann, Sebastian R Schulz, Gema Morillas Ramos, Metodi V Stankov, Hans-Martin Jäck, Georg M N Behrens, Stefan Pöhlmann, Markus Hoffmann
Journal: The Lancet Infectious Diseases (2023)
Nonalcoholic fatty liver disease and non-liver comorbidities
Authors: Richie Manikat, Mindie H. Nguyen
Journal: Clinical and Molecular Hepatology (2023)

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.
Portable evaluation of obstructive sleep apnea in adults: A systematic review
Authors: Yet H. Khor, Su-Wei Khung, Warren R. Ruehland, Yuxin Jiao, Jeremy Lew, Maitri Munsif, Yvonne Ng, Anna Ridgers, Max Schulte, Daniel Seow, William Soon, Thomas Churchward, Mark E. Howard
Journal: Sleep Medicine Reviews (2023)
Divergent and dominant anti-inflammatory effects of patient-derived anticitrullinated protein antibodies (ACPA) in arthritis development
Authors: Bruno Raposo, Marcelo Afonso, Lena Israelsson, Heidi Wähämaa, Ragnhild Stålesen, Fredrik Wermeling, Aase Haj Hensvold, Caroline Grönwall, Bence Rethi, Lars Klareskog, Vivianne Malmström
Journal: Annals of the Rheumatic Diseases (2023)
Investigating the autoregulation of applied blood flow restriction training pressures in healthy, physically active adults: an intervention study evaluating acute training responses and safety
Authors: Ewoud Jacobs, Nicholas Rolnick, Evi Wezenbeek, Lenka Stroobant, Robbe Capelleman, Nele Arnout, Erik Witvrouw, Joke Schuermans
Journal: British Journal of Sports Medicine (2023)

Objective To examine the effects of autoregulated (AUTO) and non-autoregulated (NAUTO) blood flow restriction (BFR) application on adverse effects, performance, cardiovascular and perceptual responses during resistance exercise. Methods Fifty-six healthy participants underwent AUTO and NAUTO BFR resistance exercise in a randomised crossover design using a training session with fixed amount of repetitions and a training session until volitional failure. Cardiovascular parameters, rate of perceived effort (RPE), rate of perceived discomfort (RPD) and number of repetitions were investigated after training, while the presence of delayed onset muscle soreness (DOMS) was verified 24 hours post-session. Adverse events during or following training were also monitored. Results AUTO outperformed NAUTO in the failure protocol (p&lt;0.001), while AUTO scored significantly lower for DOMS 24 hours after exercise (p&lt;0.001). Perceptions of effort and discomfort were significantly higher in NAUTO compared with AUTO in both fixed (RPE: p=0.014, RPD: p&lt;0.001) and failure protocol (RPE: p=0.028, RPD: p&lt;0.001). Sixteen adverse events (7.14%) were recorded, with a sevenfold incidence in the fixed protocol for NAUTO compared with AUTO (NAUTO: n=7 vs AUTO: n=1) and five (NAUTO) vs three (AUTO) adverse events in the failure protocol. No significant differences in cardiovascular parameters were found comparing both pressure applications. Conclusion Autoregulation appears to enhance safety and performance in both fixed and failure BFR-training protocols. AUTO BFR training did not seem to affect cardiovascular stress differently, but was associated with lower DOMS, perceived effort and discomfort compared with NAUTO. Trial registration number NCT04996680 .
Efficacy and safety of tofacitinib in patients with polymyalgia rheumatica: a phase 2 study
Authors: Le Zhang, Jun Li, Hanlin Yin, Dandan Chen, Yuan Li, Liyang Gu, Yakai Fu, Jie Chen, Zhiwei Chen, Shaoying Yang, Shuang Ye, Ting Li, Liangjing Lu
Journal: Annals of the Rheumatic Diseases (2023)

Figure 1 Enrolment and primary outcome (N=14) (A), summary of adverse events (N=14) (B) and changes of inflammatory cytokines in the 24week study (N=9) (C).GM-CSF, granulocyte-macrophage colony-stimulating factor; IL, interleukin; LEF, leflunomide; MTX, methotrexate; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor.
Public health guidelines for physical activity during pregnancy from around the world: a scoping review
Authors: Melanie Hayman, Wendy J Brown, Alison Brinson, Emily Budzynski-Seymour, Tracy Bruce, Kelly R Evenson
Journal: British Journal of Sports Medicine (2023)

Background and objective Despite the known health benefits of physical activity (PA), pregnancy is a time of marked decline in PA levels. To provide women with reliable and trustworthy information, and to encourage greater participation in PA during pregnancy, many governments have developed guidelines for PA during pregnancy. Our aim was to synthesise the most recent public health guidelines on PA during pregnancy from different countries in order to understand the nature and extent of advice that is available. Design Scoping review. Data sources Search of the grey literature, direct contact with international experts, screening of relevant academic literature and citation searching. Eligibility criteria Public health guidelines developed or endorsed by government departments published since 2010. Results Our search located 30 eligible guidelines, published in 11 different languages. There is remarkable concordance in the advice offered. For women with uncomplicated pregnancy, guidelines recommend: 150–300 min/week of moderate intensity aerobic activity; pelvic floor and muscle strengthening exercises; modification of some exercises (eg, supine position); and provide lists of warning signs to cease activity (eg, persistent dizziness, vaginal bleeding) and activities that should be avoided (eg, if high risk of falling/collision). Few guidelines offer specific advice for highly active women (eg, athletes), or trimester-specific or culturally specific considerations. Conclusions This review provides a summary of public health recommendations for PA during pregnancy around the world. The challenge is now to ensure that all who provide healthcare for women understand the guidelines and encourage safe participation in PA during pregnancy.
Transcriptional landscape of oncogene-induced senescence: a machine learning-based meta-analytic approach
Authors: Yeaeun Han, Gos Micklem, Sung Young Kim
Journal: Ageing Research Reviews (2023)

Oncogene-induced senescence (OIS) is highly heterogeneous, varying by oncogenic signals and cellular context. While its dual role, in the initial inhibition potentially later leading to promotion of tumors through the senescence-associated secretory phenotype, is still a matter of debate, it is undeniable that OIS is critical to understanding tumorigenesis. A major obstacle to OIS research is the absence of a universally accepted marker. Here, we present a robust OIS-specific transcriptomic secretory phenotype, termed oncogene-induced senescence secretory phenotype (OIS-SP), which can identify OIS across multiple biological contexts from in vitro datasets to in vivo human samples. We apply a meta-analytic machine learning pipeline to harmonize a deliberately varied selection of Ras-Raf-MEK-induced senescence datasets of differing origins, oncogenic signals and cell types. Finally we make use of bypass data to identify key genes and eliminate genes associated with quiescence, so identifying 40 OIS-SP genes. Within this set, we determined a robust core of five OIS-SP genes (FBLN1, CXCL12, EREG, CST1 and MMP10). Importantly, these 5 OIS-SP genes showed clear, consistent regulation patterns across various human Ras-Raf-MEK-mutated tumor tissues, which suggests that OIS-SP may be a novel cancer driver phenotype with an unexpectedly critical role in tumorigenesis.
Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis
Authors: Chuanlin Ding, Rejeena Shrestha, Xiaojuan Zhu, Anne E. Geller, Shouzhen Wu, Matthew R. Woeste, Wenqian Li, Haomin Wang, Fang Yuan, Raobo Xu, Julia H. Chariker, Xiaoling Hu, Hong Li, David Tieri, Huang-Ge Zhang, Eric C. Rouchka, Robert Mitchell, Leah J. Siskind, Xiang Zhang, Xiaoji G. Xu, Kelly M. McMasters, Yan Yu, Jun Yan
Journal: Nature Immunology (2023)
Re: Farnoosh Nik-Ahd, Andrew Jarjour, Jane Figueiredo, et al. Prostate-specific Antigen Screening in Transgender Patients. Eur Urol. 2023;83:48–54
Authors: Sandra García Nader, Sebastián Peña Rodríguez, Cesar Alejandro Diaz Ritter
Journal: European Urology (2023)
Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program
Authors: Molla M Wassie, Graeme P Young, Jean M Winter, Charles Cock, Peter Bampton, Mahadya Rahman, Richard Heddle, Robert Fraser, Rosie Meng, Erin L Symonds
Journal: Clinical Gastroenterology and Hepatology (2023)
Association of HSD17B13 and PNPLA3 With Liver Enzymes and Fibrosis in Hispanic/Latino Individuals of Diverse Genetic Ancestries
Authors: Stephanie M. Rutledge, Emily R. Soper, Ning Ma, Vikas Pejaver, Scott L. Friedman, Andrea D. Branch, Eimear E. Kenny, Gillian M. Belbin, Noura S. Abul-Husn
Journal: Clinical Gastroenterology and Hepatology (2023)
Revisiting autoimmune lymphoproliferative syndrome caused by Fas ligand mutations
Authors: Maria Elena Maccari, Pascal Schneider, Cristian Roberto Smulski, Andrea Meinhardt, Fernando Pinto, Luis Ignacio Gonzalez-Granado, Catharina Schuetz, Mauricio Pablo Sica, Miriam Gross, Ilka Fuchs, Patrick Kury, Maximilian Heeg, Tatjana Vocat, Laure Willen, Caroline Thomas, Regina Hühn, Aude Magerus, Myriam Lorenz, Klaus Schwarz, Frederic Rieux-Laucat, Stephan Ehl, Anne Rensing-Ehl
Journal: Journal of Allergy and Clinical Immunology (2023)
Extrinsic control of the early postnatal CA1 hippocampal circuits
Authors: Erwan Leprince, Robin F. Dard, Salomé Mortet, Caroline Filippi, Marie Giorgi-Kurz, Romain Bourboulou, Pierre-Pascal Lenck-Santini, Michel A. Picardo, Marco Bocchio, Agnès Baude, Rosa Cossart
Journal: Neuron (2023)
Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation
Authors: Ying-Yin Chao, Alisa Puhach, David Frieser, Mahima Arunkumar, Laurens Lehner, Thomas Seeholzer, Albert Garcia-Lopez, Marlot van der Wal, Silvia Fibi-Smetana, Axel Dietschmann, Thomas Sommermann, Tamara Ćiković, Leila Taher, Mark S. Gresnigt, Sebastiaan J. Vastert, Femke van Wijk, Gianni Panagiotou, Daniel Krappmann, Olaf Groß, Christina E. Zielinski
Journal: Nature Immunology (2023)

Abstract It has been shown that innate immune responses can adopt adaptive properties such as memory. Whether T cells utilize innate immune signaling pathways to diversify their repertoire of effector functions is unknown. Gasdermin E (GSDME) is a membrane pore-forming molecule that has been shown to execute pyroptotic cell death and thus to serve as a potential cancer checkpoint. In the present study, we show that human T cells express GSDME and, surprisingly, that this expression is associated with durable viability and repurposed for the release of the alarmin interleukin (IL)-1α. This property was restricted to a subset of human helper type 17 T cells with specificity for Candida albicans and regulated by a T cell-intrinsic NLRP3 inflammasome, and its engagement of a proteolytic cascade of successive caspase-8, caspase-3 and GSDME cleavage after T cell receptor stimulation and calcium-licensed calpain maturation of the pro-IL-1α form. Our results indicate that GSDME pore formation in T cells is a mechanism of unconventional cytokine release. This finding diversifies our understanding of the functional repertoire and mechanistic equipment of T cells and has implications for antifungal immunity.